Cystic echinococcosis (CE, hydatid disease) is one of the most neglected parasitic diseases of worldwide prevalence. Hydatid cysts occur mainly in the liver (70%) and the lung (20%). Clinical symptoms and signs depend on their localisation, size, and number. Currently four treatment modalities are in use: (1) surgery, (2) PAIR (puncture, aspiration, injection of protoscolicidal agent, reaspiration), (3) chemotherapy with albendazole (ABZ) or mebendazole (MBZ), and (4) watch and wait for inactive, clinically silent cysts. The evidence supporting any of the four treatment modalities is insufficient, and selecting treatment options for patients remains controversial. Investment into clinical trials for CE with an appropriate size and quality standards is urgently needed to improve care for patients suffering from this neglected disease. The specific aims of the R34 planning grant are to develop the protocol, SOPs and related trial documents for a Phase 2 clinical trial of stage-specific treatment of cystic Echinococcosis (EchinoTrial) and to select the trial sites in Peru. The main study is a pragmatic randomised controlled trial to determine the efficacy, safety and relapse rate of the four currently available treatment modalities of uncomplicated hepatic CE cysts stratified by cyst stage as defined by the WHO ultrasound classification 2002 [Phase 2 stage-specific clinical trial (main study)]. Given the extraordinary clinical complexity of CE, treatment standardization requires the exclusion of patients with complicated cysts in need of individualized therapy. Patients with complicated CE cysts (e.g. cysto-biliary fistulas, cyst rupture, secondary bacterial infection) will be investigated in a prospective observational noncomparative study arm (substudy). The trial site in Peru offers access to a highly endemic population for CE. The expected outcome of this trial will create a solid evidence base for the allocation of available treatment modalities on cyst stage level, will help to avoid unnecessary treatment of inactive cysts and will define the long term prognosis after treatment (relapse rate). PUBLIC HEALTH RELEVANCE: Cystic echinococcosis (CE) is one of the most neglected infectious diseases with an estimated global burden at over 1 million DALYs per year.1 The results of the randomized controlled trial suggested will allow to select the most appropriate treatment according to cyst stage and to base treatment efficacy, the rate of side effects and relapse rates on solid evidence. This will help to significantly reduce treatment and disease associated morbidity.